Dental caries is the most common oral infectious disease that afflicts humans. More than 95% of all adults have experienced this disease. It is more common than asthma, hay fever or chronic bronchitis in 5-17 year old children. The American public spends close to $40 billion per year to treat this disease or its consequences. Dental caries results from the interaction of specific bacteria with constituents of the diet on a susceptible tooth surface. Dental plaque accumulation is the first clinical evidence of this interaction; dental plaque is a biofilm which is comprised of a population of bacteria growing on the tooth surface enmeshed in a polysaccharide matrix. Acid can be formed rapidly by acidogenic bacteria, such as Streptococcus mutans, within the matrix and its persistence results in dissolution of the tooth. Furthermore, plaque is also the major aetiological factor in gingivitis. Cranberries, like other natural products, harbor a plethora of biological compounds such as flavonoids (e.g. quercetin and myricetin), phenolic acids (benzoic acid), anthocyanins, condensed tannins, and others. We have shown that many of these substances can: (i) inhibit enzymes associated with the formation of the plaque polysaccharide matrix, (ii) block adherence of bacteria to surfaces, (iii) prevent acid formation, and (iv) reduce acid tolerance of cariogenic organisms. For example, quercetin and myricetin are effective inhibitors of glucosyltransferases (GTFs), enzymes responsible for the synthesis of glucans; glucans synthesized by GTFs mediate the adherence and accumulation of cariogenic streptococci on the tooth surface. Weak acids, such as benzoate (benzoic acid), affect the acid production by S. mutans and have been shown to reduce dental caries in rats. We propose a comprehensive plan to explore the influence of cranberry on many of the biological aspects involved in the pathogenesis of dental plaque formation and caries. We also propose to examine the ability of cranberry to prevent or reduce caries in our well-proven rodent model and to investigate the effects of cranberry on plaque formation and gingivitis in vivo.